Women living far away from a radiotherapy centre find it difficult to take the radiotherapy following breast conserving surgery. Many choose mastectomy to avoid these extra 30 hospital visits.

Upto 1/3 of radiotherapy units' workload world-wide is breast cancer. This can lead to unacceptably long waiting lists. Any reduction in radiotherapy time could have significant reduction in financial and patient costs.

Upto 50% of local recurrence may be attributable to ‘geographical miss’ - of the boost dose. Accurate targeting of radiotherapy is important.

A miniature electron generator and accelerator that delivers soft (50KV) x-rays from within the breast There is quick attenuation (~1/r3) so ‘very-high-dose’ region is small and shielding is easyThe pliable breast tissue wraps around the applicator achieving true conformal brachytherapy. The procedure is performed in a standard operation theatre in about 25-30 min

The international randomised trial

If Targit is proven equivalent to conventional radiotherapy, then... Post-operative radiotherapy could be avoided in many women sparing them of the ordeal of 6 weeks of daily visits to the radiotherapy centre Breast conserving therapy will be available to more women in remote areas, the whole local treatment being delivered in one sitting. Tumour bed boost would be delivered accurately to all patients, potentially reducing local recurrence rates This is modern technology that could actually save money- up to 15 million pounds in UK alone

References 1. Vaidya et al Br J Cancer 1996;74:840. 2. Fisher et al Sem Surg Oncol 1992;8:161. 3. Veronesi et al N Engl J Med 1993;328:1587. 4. Vaidya et al Ann Oncol 2001;12:1075.

INTRABEAM is a trademark of Photoelectron Corporation PeC, USA

Patients and methodsPatients suitable for breast conserving surgery received wide local excision + Axillary surgery followed by Targeted intra-operative radiotherapy with Intrabeam (5Gy @1cm~10Gy @0.5cm). The protocol included a single dose of peri-operative antibiotic. Most patients received post-operative whole breast radiotherapy the tumour-bed receiving no boost, but with no special shielding. 91 patients have been treated with this technique in pilot studies. Of these 12 patients have not received any other form of radiotherapyResultsNo major complications. One patient (No.3) had a small area of radionecrosis of skin (the applicator was too close to the skin). We have since modified the technique to ensure that the skin or dermis does not come too close to the applicator especially while taking the purse string suture. One other patient, aged 80yrs, had delayed wound healing. In the Australian series peri-operative antibiotics were not given and there was a significant wound infection rate (2/16). There was only 1 wound infection among rest of the patients.Good cosmetic results. The cosmetic outcome was good. Mean patient satisfaction index (formally calculated for the UK patients) by dividing the observed by the expected score for appearance and texture (O/E) was 1.2 (95%CI 1.0-1.4), meaning that almost all patients were satisfied with the cosmetic outcome.No local recurrence. There has been no local recurrence. The median follow times are 36m (UK), 10m (OZ) and 17m (USA). The maximum follow up is 48 months.

Occult cancer

Primary tumour

Targit with PRS

Estimated Biologically equivalent radiation dose (BED)

2mm e.g. breast

12Gy 53Gy

10mm e.g. skin

12Gy 7Gy

Distance from applicator

ExternalBoost

The Problems with Post-operative Radiotherapy

The Solution and its Rationale

The Novel Technique - Intrabeam™

Pilot studies

/=10 /=1.5

121Gy

21Gy

UK4, Australia & USA to test feasibility, safety & efficacy

Solution To irradiate the peri-tumoural tissues intra-operatively in a single fraction.Rationale 91% of local recurrence after breast conserving therapy occurs near the site of the primary tumour1,2,3, even when radiotherapy is not given. This is despite the finding on whole organ analysis of mastectomy specimens that 63% harbour occult cancers, 80% of which are situated remote from the index quadrant1 Thus, the tumours in other quadrants may remain dormant, never becoming clinically relevant; and radiotherapy to the site of the original tumour may be adequate.

Electron beam drift

tube

Electron target & X-ray source

Shielding cap

Applicator shank

SkinApplicator sphere

Breast tissueChest wall

Schematic diagram of the applicator in

tumour bed

Whole organ analysis

Main outcome: local recurrenceSecondary outcomes: cosmesis, patient satisfaction, cost32 patients have been randomised in the UK centre so far

Targeted Intraoperative radiotherapy (TARGIT) with additional external beam radiotherapy in

selected cases*

Conventional 6-week

postoperative radiotherapy

vs.

*for patients at high risk of local recurrence eg. Lobular cancers, EIC, young age, T >2cm, N>0, etc.